Low brain penetrant CB1 receptor agonists for the treatment of neuropathic pain.

Novel, low brain penetrant, orally bioavailable CB1 receptor agonists were designed using calculated polar surface area as a predictor of CNS permeability. This approach led to the discovery of LBP1, an orally bioavailable, low brain penetrant CB1 receptor agonist with robust activity in rodent models of neuropathic pain and a good preclinical therapeutic profile.